A phase II trial of Abiraterone followed by randomization to addition of Dasatinib or Sunitinib in men with metastatic castration resistant prostate cancer.

Abstract Background Resistance to novel androgen signalling inhibition and metastatic castration resistant prostate cancer (mCRPC) progression is likely dependent on tumor microenvironment interactions. The Src pathway and neoangiogenesis have been implicated in prostate cancer progression. We studied the effect of adding the targeted agents Dasatinib and Sunitinib to Abiraterone acetate (AA) in men with mCRPC. Patients and Methods In this open-label, randomized, phase II study, mCRPC patients received AA. Upon resistance to AA, they were randomized 1:1 to combination with (AA-D) Dasatinib or (AA-S) Sunitinib. Upon second progression, patients crossed over. Primary endpoint was time to treatment failure (TTF), defined as time to progression or death. Secondary endpoints included overall survival (OS) and safety. Results From 03/2011 to 02/2015, 179 patients were enrolled and 132 subsequently randomized. Median TTF was 5.7 months in the Dasatinib and 5.5 months in the Sunitinib group. There was no difference between the two groups in terms of TTF (Hazard ratio (HR) 0.85, 95% Confidence Interval (CI) 0.59- 1.22). Median OS from study entry was 26.3 months in the Dasatinib group and 27.7 months in the Sunitinib group (HR 1.02, 95% CI 0.71- 1.47). Adverse events ≥Grade 3 related to study medication were more frequent with Sunitinib (n=44, 46%) compared to Dasatinib (n=26, 24%). At data cut off, 7 patients were demonstrating a continuous response to AA, with a median duration of treatment 5.7 years. Conclusion There is no difference in OS and TTF between Dasatinib and Sunitinb combined with Abiraterone in the treatment of patients with bone mCRPC.